Major Advance Extends Time for Intervention after Stroke

Researchers have discovered a way to extend how long clinicians have to reverse a stroke caused by a large clot blocking an artery in the brain. Traditionally, mechanical thrombectomy — the endovascular retrieval and removal of a clot — had to be performed within six hours of when the stroke patient last felt well. Now a new multicenter trial has shown that a combination of special brain imaging and reperfusion — restoration of blood flow — helps to identify stroke sufferers who can receive benefit for up to 24 hours.

“The extension of the window from six hours to 24 hours is earth-shaking. So many more people will be able to receive treatment,” said Dileep R. Yavagal, M.D., professor of clinical neurology and neurosurgery, and chief of interventional neurology at the University of Miami Miller School of Medicine.

The University of Miami/Jackson Memorial Hospital site was one of the top enrollers in the “DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN)” study. The findings of the study were published on November 11 in the New England Journal of Medicine.

Even though earlier remains better for these medical emergencies, the study offers hope to patients who speed to an emergency room beyond the previous six-hour deadline. This is important, “because a lot of strokes occur at night, and sometimes people don’t realize they’ve had one until they wake up hours later,” added Yavagal, who was principal investigator for the UM/Jackson study site.

“This new study adds another major game-changer in the way we will be able to treat acute stroke,” said Ralph L. Sacco, M.D., M.S., professor and chair of neurology and Olemberg Chair in Neurological Disorders at the Miller School. “Time is still brain, and we need to get people to stroke centers as quickly as possible, but with brain imaging and these new devices we can make a remarkable difference for our patients.”

Less disability and improved function

Yavagal, his co-principal investigator, Amer Malik, M.D., M.B.A., assistant professor of neurology and chief of the Neurohospitalist Section at UM/Jackson, and a team of international investigators randomly assigned 107 stroke patients to mechanical thrombectomy and another 99 to standard medical care from September 2014 through February 2017. They found the endovascular removal of the brain clot was associated with significantly less disability at 90 days (5.5 vs. 3.4 in the standard medical care group on the utility-weighted modified Rankin Scale; 0 is death and 10 is no disability).

At the same time, the proportion of patients who were functionally independent at 90 days was also significantly higher in the thrombectomy group compared to controls, 48.6 percent versus 13.3 percent, on the modified Rankin scale. All the secondary outcomes the researchers evaluated also favored the intervention group.

Importantly, mechanical thrombectomy appears just as safe when performed in the six- to 24-hour timeframe, compared to patients treated up to six hours. The study revealed no significant differences in rates of symptomatic intracerebral hemorrhage or deaths between these groups.

The findings not only support use of mechanical thrombectomy, but also advance the field by showing that diffusion MRI or perfusion CT can identify candidates for the later intervention window. The trial demonstrated this strategy can improve outcomes for stroke patients with a “clinical mismatch” — in other words, people who present with small- to medium-size infarct area surrounded by a larger brain region that can be reperfused.

Potential to help more stroke sufferers

The larger window of time to intervene addresses a real need for patients with these disabling large vessel occlusions.

“In the past when we only had tPA, there was a less than 25 percent chance of opening these large clots and was only applicable up to 4.5 hours after stroke symptom onset,” Yavagal said. “With perfusion imaging, we can find a lot more people who could benefit by avoiding long-term stroke disability.”

The techniques used in the study require referral of patients to a stroke center. Going forward, however, the researchers want to see if less sophisticated imaging modalities could make this approach more widely available.

In addition, “now that we’ve proven this in patients with a significant amount of salvageable brain, we want to push it further to people with less salvageable presentations, to see if they will have the same benefit,” Yavagal said. He would also like to study if addition of mesenchymal stem cells to a reperfused brain can boost recovery even further.